{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:51:41Z","timestamp":1785941501948,"version":"3.56.0"},"reference-count":39,"publisher":"American Chemical Society (ACS)","issue":"8","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R33 CA267226"],"award-info":[{"award-number":["R33 CA267226"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["F30DK142473"],"award-info":[{"award-number":["F30DK142473"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30 DK123704"],"award-info":[{"award-number":["P30 DK123704"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"SmartState Centers of Economic Excellence","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Office of the Assistant Secretary of Defense for Health Affairs","doi-asserted-by":"publisher","award":["W81XWH-22-1-0330"],"award-info":[{"award-number":["W81XWH-22-1-0330"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lupus nephritis (LN) and diabetic nephropathy (DN) are leading causes of kidney failure, characterized by distinct yet overlapping patterns of glomerular injury. While histopathology remains central to diagnosis, it provides limited insight into the underlying molecular remodeling. Here, we applied matrix-assisted laser desorption\/ionization mass spectrometry imaging (MALDI-MSI) to define the spatial N-glycan landscape across human kidney biopsies from healthy controls (HCs) and patients with DN or LN. Whole-biopsy analyses demonstrated that identical N-glycan species adopt distinct spatial distributions depending on the disease context. Healthy kidneys were enriched in bisected N-glycans, DN in biantennary and sialylated species, and LN in fucosylated and paucimannose N-glycans, reflecting divergent enzymatic and pathogenic pathways. Glomerulus-resolved analyses substantially enhanced discrimination among disease groups, revealing previously undetected differences and highlighting disease-specific molecular phenotypes that were masked at the whole biopsy level. Notably, glomeruli classified as histologically normal exhibited distinct N-glycan signatures across disease states, indicating that molecular remodeling occurs independently of the overt structural changes. Within biopsies, N-glycan class composition shifted systematically with glomerular injury, with DN displaying more uniform remodeling and LN demonstrating greater phenotypic heterogeneity. Mixed-effect modeling confirmed significant morphology-dependent differences while accounting for biopsy-level clustering. MALDI-IHC analysis further supported phenotype-specific molecular differences across the glomerular subtypes. Collectively, these findings establish glomerular N-glycan architecture as a major driver of glycomic divergence across kidney diseases and position spatial N-glycomics as a translational approach for defining disease-specific molecular signatures within intact renal tissues.<\/jats:p>","DOI":"10.1021\/jasms.6c00163","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T06:44:46Z","timestamp":1784702686000},"page":"1952-1963","source":"Crossref","is-referenced-by-count":0,"title":["N-Glycan MALDI\nMSI Differentiates Kidney Glomerular\nDisease Phenotypes"],"prefix":"10.1021","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9945-4085","authenticated-orcid":true,"given":"Aaron O.","family":"Angerstein","sequence":"first","affiliation":[{"name":"Medical University of South Carolina , , 173 Ashley Ave , , ,","place":["Charleston, South Carolina, United States, 29425"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishwajeeth","family":"Pasham","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina , , , ,","place":["Charleston, South Carolina, United States, 29425"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Kittrell","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina , , 173 Ashley Ave , , ,","place":["Charleston, South Carolina, United States, 29425"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2152-5469","authenticated-orcid":true,"given":"Shana M.","family":"Coley","sequence":"additional","affiliation":[{"name":"Arkana Laboratories , 10810 Executive Center Dr. Suite 100 , , ,","place":["Little Rock, Arkansas, United States, 72211"]},{"name":"NYU Langone Health , 550 first Avenue, Suite 461 , , ,","place":["New York, New York, United States, 10016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara K.","family":"Nowling","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina , , 171 Ashley Avenue , , ,","place":["Charleston, South Carolina, United States, 29425"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard R.","family":"Drake","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina , , 173 Ashley Ave , , ,","place":["Charleston, South Carolina, United States, 29425"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"2026080510110310600_cit1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.765356","article-title":"New Endothelial Mechanisms in Glomerular\n(Patho)biology and Proteinuria Development Captured by Intravital\nMultiphoton Imaging","volume":"8","author":"Gyarmati","year":"2021","journal-title":"Front. Med. (Lausanne)"},{"issue":"15","key":"2026080510110310600_cit2","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1056\/NEJMra1808786","article-title":"Insights into Glomerular\nFiltration and Albuminuria","volume":"384","author":"Benzing","year":"2021","journal-title":"N. Engl. J. Med."},{"issue":"6","key":"2026080510110310600_cit3","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1038\/s41581-019-0129-4","article-title":"Glycosylation in health\nand disease","volume":"15","author":"Reily","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"2026080510110310600_cit4","article-title":"Essentials of\nGlycobiology","volume-title":"Essentials of Glycobiology","author":"Varki","year":"2022","edition":"4"},{"issue":"5","key":"2026080510110310600_cit5","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1097\/01.ASN.0000013297.11876.5B","article-title":"N-Linked Glycosylation\nIs Critical for the Plasma Membrane Localization of Nephrin","volume":"13","author":"Yan","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"2026080510110310600_cit6","doi-asserted-by":"publisher","DOI":"10.1093\/pcmedi\/pbaf017","article-title":"Glycosylation\nin kidney diseases","volume":"8","author":"Ling","year":"2025","journal-title":"Precision Clin. Med."},{"key":"2026080510110310600_cit7","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.766689","article-title":"The Glomerular Endothelium Restricts\nAlbumin Filtration","volume":"8","author":"Ballermann","year":"2021","journal-title":"Front. Med."},{"key":"2026080510110310600_cit8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1251876","article-title":"Endothelial\ncell activation and glycocalyx shedding\n- potential as biomarkers in patients with lupus nephritis","volume":"14","author":"Yung","year":"2023","journal-title":"Front. Immunol."},{"key":"2026080510110310600_cit9","doi-asserted-by":"publisher","first-page":"1886","DOI":"10.1681\/ASN.2019020192","article-title":"Glomerular Function\nand Structural Integrity Depend on Hyaluronan Synthesis by Glomerular\nEndothelium","volume":"30","author":"van den Berg","year":"2019","journal-title":"J. Am. Soc. Nephrol."},{"key":"2026080510110310600_cit10","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1053\/j.ajkd.2017.10.026","article-title":"Update on Diabetic Nephropathy: Core Curriculum 2018","volume":"71","author":"Umanath","year":"2018","journal-title":"Am. J. Kidney Dis."},{"key":"2026080510110310600_cit11","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1053\/j.ajkd.2019.10.017","article-title":"Update\non Lupus\nNephritis: Core Curriculum 2020","volume":"76","author":"Parikh","year":"2020","journal-title":"Am. J. Kidney\nDis."},{"key":"2026080510110310600_cit12","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1111\/j.1523-1755.2004.00443.x","article-title":"The classification of\nglomerulonephritis in systemic lupus erythematosus revisited","volume":"65","author":"Weening","year":"2004","journal-title":"Kidney Int."},{"key":"2026080510110310600_cit13","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1681\/ASN.2010010010","article-title":"Pathologic classification of diabetic nephropathy","volume":"21","author":"Tervaert","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"issue":"9","key":"2026080510110310600_cit14","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1681\/ASN.0000000000000393","article-title":"Protein N-Glycans in\nHealthy and Sclerotic Glomeruli in Diabetic Kidney Disease","volume":"35","author":"Velic\u030ckovic\u0301","year":"2024","journal-title":"J. Am. Soc. Nephrol."},{"key":"2026080510110310600_cit15","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.976298","article-title":"Mass spectrometry-based\nN-glycosylation\nanalysis in kidney disease","volume":"9","author":"Ren","year":"2022","journal-title":"Front. Mol. Biosci."},{"issue":"6","key":"2026080510110310600_cit16","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1681\/ASN.2014050508","article-title":"Renal Glycosphingolipid\nMetabolism\nIs Dysfunctional in Lupus Nephritis","volume":"26","author":"Nowling","year":"2015","journal-title":"J. Am.\nSoc. Nephrol."},{"issue":"4","key":"2026080510110310600_cit17","doi-asserted-by":"publisher","first-page":"F630","DOI":"10.1152\/ajprenal.00421.2017","article-title":"Neuraminidase activity mediates IL-6 production by\nactivated lupus-prone mesangial cells","volume":"314","author":"Sundararaj","year":"2018","journal-title":"Am. J.\nPhysiol.: Renal Physiol."},{"key":"2026080510110310600_cit18","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2025.151581","article-title":"Spatial\nGlycomics and Kidney Disease","volume":"44","author":"Velic\u030ckovic\u0301","year":"2024","journal-title":"Semin. Nephrol."},{"issue":"3","key":"2026080510110310600_cit19","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.100747","article-title":"Protocol for multimodal analysis of human kidney\ntissue by imaging mass spectrometry and CODEX multiplexed immunofluorescence","volume":"2","author":"Neumann","year":"2021","journal-title":"STAR Protoc."},{"issue":"24","key":"2026080510110310600_cit20","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adu3730","article-title":"A lipid atlas of the\nhuman kidney","volume":"11","author":"Farrow","year":"2025","journal-title":"Sci. Adv."},{"issue":"2","key":"2026080510110310600_cit21","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.kint.2024.11.008","article-title":"In situ\nmolecular profiles\nof glomerular cells by integrated imaging mass spectrometry and multiplexed\nimmunofluorescence microscopy","volume":"107","author":"Esselman","year":"2025","journal-title":"Kidney Int."},{"key":"2026080510110310600_cit22","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2025.344724","article-title":"Spatial atlasing of\nN-glycosylation in healthy control and clear cell renal cell carcinoma\ntissues linked with immune checkpoint inhibition response by MALDI\nmass spectrometry imaging","volume":"1380","author":"Kittrell","year":"2025","journal-title":"Anal. Chim. Acta"},{"key":"2026080510110310600_cit23","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-50957-w","article-title":"An N-glycome\ntissue atlas of 15 human normal and cancer tissue types determined\nby MALDI-imaging mass spectrometry","volume":"14","author":"Wallace","year":"2024","journal-title":"Sci. Rep."},{"key":"2026080510110310600_cit24","doi-asserted-by":"publisher","DOI":"10.1002\/jms.4490","article-title":"Defining the human kidney\nN-glycome in normal\nand cancer tissues using MALDI imaging mass spectrometry","volume":"55","author":"Drake","year":"2020","journal-title":"J. Mass Spectrom."},{"issue":"4","key":"2026080510110310600_cit25","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1021\/jasms.0c00473","article-title":"Highly Multiplexed\nImmunohistochemical MALDI-MS Imaging of Biomarkers in Tissues","volume":"32","author":"Yagnik","year":"2021","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"28","key":"2026080510110310600_cit26","doi-asserted-by":"publisher","first-page":"7011","DOI":"10.1007\/s00216-023-04983-2","article-title":"Evaluation\nof antibody-based\nsingle cell type imaging techniques coupled to multiplexed imaging\nof N-glycans and collagen peptides by matrix-assisted laser desorption\/ionization\nmass spectrometry imaging","volume":"415","author":"Dunne","year":"2023","journal-title":"Anal. Bioanal. Chem."},{"key":"2026080510110310600_cit27","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1337319","article-title":"Utilizing multimodal mass spectrometry\nimaging for profiling immune cell composition and N-glycosylation\nacross colorectal carcinoma disease progression","volume":"14","author":"Young","year":"2024","journal-title":"Front. Pharmacol."},{"issue":"1","key":"2026080510110310600_cit28","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath:\nOpen source\nsoftware for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci. Rep."},{"issue":"2","key":"2026080510110310600_cit29","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.ijms.2006.09.027","article-title":"MALDI-TOF\nand cluster-TOF-SIMS imaging of Fabry disease biomarkers","volume":"260","author":"Touboul","year":"2007","journal-title":"Int. J. Mass Spectrom."},{"key":"2026080510110310600_cit30","doi-asserted-by":"publisher","first-page":"9364","DOI":"10.1021\/acs.analchem.1c00649","article-title":"High-Resolution\nHuman Kidney Molecular Histology by Imaging Mass Spectrometry of Lipids","volume":"93","author":"Marti\u0301n-Saiz","year":"2021","journal-title":"Anal. Chem."},{"key":"2026080510110310600_cit31","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.ebiom.2016.03.033","article-title":"Mass Spectrometry Imaging\nReveals Elevated Glomerular ATP\/AMP in Diabetes\/obesity and Identifies\nSphingomyelin as a Possible Mediator","volume":"7","author":"Miyamoto","year":"2016","journal-title":"EBioMedicine"},{"key":"2026080510110310600_cit32","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1194\/jlr.M049189","article-title":"Diabetic nephropathy\ninduces alterations in the glomerular and tubule lipid profiles","volume":"55","author":"Grove","year":"2014","journal-title":"J. Lipid Res."},{"issue":"7","key":"2026080510110310600_cit33","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1021\/jasms.3c00033","article-title":"Microscopy-Directed\nImaging Mass Spectrometry for Rapid High Spatial Resolution Molecular\nImaging of Glomeruli","volume":"34","author":"Esselman","year":"2023","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"2026080510110310600_cit34","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1093\/jb\/mvaf033","article-title":"Bisecting GlcNAc modification\nof angiotensin-related glycoproteins in mouse kidney","volume":"178","author":"Kawade","year":"2025","journal-title":"J. Biochem."},{"issue":"2","key":"2026080510110310600_cit35","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21020437","article-title":"3D Structure and Function\nof Glycosyltransferases Involved in N-glycan Maturation","volume":"21","author":"Nagae","year":"2020","journal-title":"Int. J. Mol. Sci."},{"issue":"9","key":"2026080510110310600_cit36","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.147789","article-title":"Aberrantly glycosylated\nIgG elicits pathogenic signaling\nin podocytes and signifies lupus nephritis","volume":"6","author":"Bhargava","year":"2021","journal-title":"JCI Insight"},{"key":"2026080510110310600_cit37","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1002\/art.41768","article-title":"Protein Mannosylation as a Diagnostic and Prognostic\nBiomarker of Lupus Nephritis: An Unusual Glycan Neoepitope in Systemic\nLupus Erythematosus","volume":"73","author":"Alves","year":"2021","journal-title":"Arthritis Rheumatol."},{"key":"2026080510110310600_cit38","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1111\/j.1365-2567.2008.02898.x","article-title":"Alteration of N-glycosylation in the kidney in a mouse\nmodel of systemic lupus erythematosus: relative quantification of\nN-glycans using an isotope-tagging method","volume":"126","author":"Hashii","year":"2009","journal-title":"Immunology"},{"issue":"10","key":"2026080510110310600_cit39","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/s41423-023-01074-1","article-title":"Immune\nregulatory networks coordinated by glycans and glycan-binding proteins\nin autoimmunity and infection","volume":"20","author":"Pinho","year":"2023","journal-title":"Cell. Mol. Immunol."}],"container-title":["Journal of the American\nSociety for Mass Spectrometry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/jasms.6c00163","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jamsef\/article-pdf\/37\/8\/1952\/66115703\/jasms.6c00163.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jamsef\/article-pdf\/37\/8\/1952\/66115703\/jasms.6c00163.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:14:17Z","timestamp":1785939257000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jamsef\/article\/37\/8\/1952\/5226249\/N-Glycan-MALDI-MSI-Differentiates-Kidney"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":39,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,7,22]]},"published-print":{"date-parts":[[2026,8,5]]}},"URL":"https:\/\/doi.org\/10.1021\/jasms.6c00163","relation":{},"ISSN":["1044-0305","1879-1123"],"issn-type":[{"value":"1044-0305","type":"print"},{"value":"1879-1123","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]}}}